Affitech

Engineering Human Antibodies | In vitro Display | Troybodies | Pepbodies

Troybodies™ is a novel "cellular" vaccine technology applicable to the treatment of cancer and infectious diseases. Partial breakdown of antibodies by antigen presenting cells (APCs) yield short peptides that are presented by MHC classII molecules to CD4 positive T-cells. This mechanism of epitope presentation was exploited by the Troybody™ concept to develop new vaccines. Troybodies™ are genetically engineered recombinant antibodies in which T-cell epitopes are inserted as loops between beta-strands in Ig constant domains, and new V-regions are added which allowing the targeting of the Troybodies™ to specific antigen presenting cells. Troybodies™ undergo endocytosis in APCs followed by partial breakdown of the molecules. As a result, T cell epitopes are liberated and are presented on MHC

Like a Trojan horse, troybodies can specifically enter an APC. Troybodies are degraded releasing the T-cell specific epitopes which are subsequently presented on the cell surface as a gateway for the activation of CD4+ T-cells.

molecules on the APC surface to efficiently stimulate T cells. The insertion of T-cell specific epitope(s) in the constant region of Ig allows the antigen binding property of the antibody to be retained. Thus, the specificity of the Troy-body can be directed towards any professional APC such as Dendritic cells or B-cells. Indeed, in in vitro and in vivo model systems, IgD specific Troybodies, directed against B-cells, were able to turn these APCs into 1000 times more potent stimulators of T cells as compared to unspecific delivery of the same T-cell epitope (2).

References:
1.Lunde et.al. (1998). ”Immunoglobulin as a vehicle for foreign antigenic peptides immunogenic to T cells” Molecular Immunology 34; 1167-1176.
2. Lunde et.al. (1999) ”Antibodies equipped with IgD-specificity efficiently deliver integrated T cell epitopes for antigen presentation by B cells” Nature Biotechnology 17; 670-675.
3. Eidem et.al. (2000) “Recombinant antibodies as carrier proteins for sub-unit vaccines: Influence and mode of fusion on protein production and T-cell activation” Journal of Immunological Methods, 245; 119-131.